Transcriptional regulation of microRNA-100, -146a, and -150 genes by p53 and NFκB p65/RelA in mouse striatal STHdh(Q7)/ Hdh(Q7) cells and human cervical carcinoma HeLa cells

RNA Biology
Jayeeta Ghose, Nitai P Bhattacharyya

Abstract

MicroRNA (miRNA) genes generally share many features common to those of protein coding genes. Various transcription factors (TFs) and co-regulators are also known to regulate miRNA genes. Here we identify novel p53 and NFκB p65/RelA responsive miRNAs and demonstrate that these 2 TFs bind to the regulatory sequences of miR-100, -146a and -150 in both mouse striatal and human cervical carcinoma cells and regulate their expression. p53 represses the miRNAs while NFκB p65/RelA induces them. Further, we provide evidence that exogenous p53 inhibits NFκB p65/RelA activity by reducing its nuclear content and competing with it for CBP binding. This suggests for the existence of a functional cross-talk between the 2 TFs in regulating miRNA expression. Moreover, promoter occupancy assay reveals that exogenous p53 excludes NFκB p65/RelA from its binding site in the upstream sequence of miR-100 gene thereby causing its repression. Thus, our work identifies novel p53 and NFκB p65/RelA responsive miRNAs in human and mouse and uncovers possible mechanisms of co-regulation of miR-100. It is to be mentioned here that cross-talks between p53 and NFκB p65/RelA have been observed to define the outcome of several biological processes and that the pr...Continue Reading

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Citations

Oct 16, 2012·Progress in Neurobiology·Rory JohnsonNoel J Buckley
Mar 4, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Michel DesjarlaisAlain Rivard
Jul 28, 2019·Cell Communication and Signaling : CCS·Shagun PoddarMalabika Datta
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Jul 3, 2020·European Journal of Pharmacology·Mohammad Amir MishanAbouzar Bagheri
Dec 19, 2020·Molecular Therapy. Nucleic Acids·Giusy RussomannoBeata Wojciak-Stothard

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Methods Mentioned

BETA
immunoprecipitation
transfection
PCR
ChIP
co-immunoprecipitation
immunoprecipitation assay
transfections
Fluoresence

Software Mentioned

Primer3
UCSC Genome Browser
Graphpad QuickCalcs
SDS
Image Master VDS

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